title: Cytosolic phospholipase A2 as a molecular target for the radiosensitization of ovarian cancer.
abstract: In ovarian cancer, the molecular targeted chemotherapeutics could increase the efficiency of low-dose radiotherapy while decreasing injury to adjusted organs. In irradiated A2780 human ovarian carcinoma cells, cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF(3) prevented activation of pro-survival Akt signaling and enhanced cell death. The potential molecular mechanisms of this effect could involve signaling through lysophosphatidic acid receptors. In the heterotopic A2780 tumor model using nude mice, cPLA(2) inhibition significantly delayed tumor growth compared to treatment with radiation or vehicle alone. These results identify cPLA(2) as a molecular target to enhance the therapeutic ratio of radiation in ovarian cancer.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Rachael R
authors.initials: RR
authors.lastname: Schulte
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Linkous
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Hallahan
authors.forename: Eugenia M
authors.initials: EM
authors.lastname: Yazlovitskaya
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000532:radiotherapy; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology*; D015153:Blotting, Western; D003131:Combined Modality Therapy; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000532:radiotherapy; D054510:Phospholipases A2, Cytosolic / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D011838:Radiation-Sensitizing Agents; C081565:arachidonyltrifluoromethane; D054510:Phospholipases A2, Cytosolic